Dopaminergic Modulation of Striatal Inhibitory Transmission and Long-Term Plasticity (original) (raw)
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Dopaminergic Modulation of Striatal Inhibitory Transmission
Dopamine (DA) modulates glutamatergic synaptic transmission and its plasticity in the striatum; however it is not well known how DA modulates long-term plasticity of striatal GABAergic inhibitory synapses. This work focused on the analysis of both dopaminergic modulation of inhibitory synapses and the synaptic plasticity established between GABAergic afferents to medium spiny neurons (MSNs). Our results showed that low and high DA concentrations mainly reduced the amplitude of inhibitory synaptic response; however detailed analysis of the D1 and D2 participation in this modulation displayed a wide variability in synaptic response. Analyzing DA participation in striatal GABAergic plasticity we observed that high frequency stimulation (HFS) of GABAergic interneurons in the presence of DA at a low concentration (200 nM) favored the expression of inhibitory striatal LTD, whereas higher concentration of DA (20 𝜇M) primarily induced LTP. Interestingly, the plasticity induced in an animal model of striatal degeneration mimicked that induced in the presence of DA at a high concentration, which was not abolished with D2 antagonist but was prevented by PKA blocker.
Dopaminergic control of synaptic plasticity in the dorsal striatum
European Journal of Neuroscience, 2001
Cortical glutamatergic and nigral dopaminergic afferents impinge on projection spiny neurons of the striatum, providing the most signi®cant inputs to this structure. Isolated activation of glutamate or dopamine (DA) receptors produces short-term effects on striatal neurons, whereas the combined stimulation of both glutamate and DA receptors is able to induce long-lasting modi®cations of synaptic excitability. Repetitive stimulation of corticostriatal ®bres causes a massive release of both glutamate and DA in the striatum and, depending on the glutamate receptor subtype preferentially activated, produces either long-term depression (LTD) or long-term potentiation (LTP) of excitatory synaptic transmission. D1-like and D2-like DA receptors interact synergistically to allow LTD formation, while they operate in opposition during the induction phase of LTP. Corticostriatal synaptic plasticity is severely impaired after chronic DA denervation and requires the stimulation of DARPP-32, a small protein expressed in dopaminoceptive spiny neurons which acts as a potent inhibitor of protein phosphatase-1. In addition, the formation of LTD and LTP requires the activation of PKG and PKA, respectively, in striatal projection neurons. These kinases appear to be stimulated by the activation of D1-like receptors in distinct neuronal populations.
Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses
Proceedings of The National Academy of Sciences, 2007
Dopaminergic modulation of short-term synaptic plasticity in fast-spiking interneurons of primate dorsolateral prefrontal cortex. . Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term excitatory postsynaptic potential (EPSP) depression. The D1 receptor agonist SKF81297 (5 M) significantly reduced the amplitude of the first EPSP but not of subsequent responses in EPSP trains, which still displayed significant depression. Dopamine (DA; 10 M) effects were similar to those of SKF81297 and were abolished by the D1 antagonist SCH23390 (5 M), indicating a D1 receptor-mediated effect. DA did not alter miniature excitatory postsynaptic currents, suggesting that its effects were activity dependent and presynaptic action potential dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells, contribution of N-methyl-D-aspartate receptors to EPSPs at subthreshold potentials was not significant and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 s suggests that in fast-spiking neurons, DA reduces the amplitude of EPSPs evoked at low frequency but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spiketiming-dependent temporal codes contained in presynaptic spike trains. Thus DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.
BMC neuroscience, 2006
The striatal complex is the major target of dopamine action in the CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the neurons in the area, form a mutually inhibitory synaptic network that is modulated by dopamine. When put in culture, the neurons reestablish this network. In particular, they make autaptic connections that provide access to single, identified medium-spiny to medium-spiny neuron synaptic connections. We examined medium-spiny neuron autaptic connections in postnatal cultures from the nucleus accumbens, the ventral part of the striatal complex. These connections were subject to presynaptic dopamine modulation. D1-like receptors mediated either inhibition or facilitation, while D2-like receptors predominantly mediated inhibition. Many connections showed both D1 and D2 modulation, consistent with a significant functional colocalization of D1 and D2-like receptors at presynaptic sites. These same connections were subject to GABAA, GABAB, norepine...
The Journal of Physiology, 2008
Reciprocally connected glutamatergic subthalamic nucleus (STN) and GABAergic external globus pallidus (GP) neurons normally exhibit weakly correlated, irregular activity but following the depletion of dopamine in Parkinson's disease they express more highly correlated, rhythmic bursting activity. Patch clamp recording was used to test the hypothesis that dopaminergic modulation reduces the capability of GABAergic inputs to pattern 'pathological' activity in STN neurons. Electrically evoked GABA A receptor-mediated IPSCs exhibited activity-dependent plasticity in STN neurons, i.e. IPSCs evoked at frequencies between 1 and 50 Hz exhibited depression that increased with the frequency of activity. Dopamine, the D 2 -like dopamine receptor agonist quinpirole and external media containing a low [Ca 2+ ] reduced both the magnitude of IPSCs evoked at 1-50 Hz and synaptic depression at 10-50 Hz. Dopamine/quinpirole also reduced the frequency but not the amplitude of miniature IPSCs recorded in the presence of tetrodotoxin. D 1 -like and D 4 agonists were ineffective and D 2/3 but not D4 receptor antagonists reversed the effects of dopamine or quinpirole. Together these data suggest that presynaptic D 2/3 dopamine receptors modulate the short-term dynamics of GABAergic transmission in the STN by lowering the initial probability of transmitter release. Simulated GABA A receptor-mediated synaptic conductances representative of control or modulated transmission were then generated in STN neurons using the dynamic clamp technique. Dopamine-modulated transmission was less effective at resetting autonomous activity or generating rebound burst firing than control transmission. The data therefore support the conclusion that dopamine acting at presynaptic D 2 -like receptors reduces the propensity for GABAergic transmission to generate correlated, bursting activity in STN neurons.
Diversity in long-term synaptic plasticity at inhibitory synapses of striatal spiny neurons
Learning & Memory, 2009
Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term potentiation (LTP) at synapses among spiny neurons (intrinsic striatal circuitry); a postsynaptically dependent long-term depression (LTD) at synapses between spiny and pallidal neurons (indirect pathway); and a presynaptically dependent LTP at strionigral synapses (direct pathway). Interestingly, long-term synaptic plasticity differs at these synapses. The functional consequences of these long-term plasticity variations during learning of procedural memories are discussed.
Homeostatic Plasticity of Striatal Neurons Intrinsic Excitability following Dopamine Depletion
The striatum is the major input structure of basal ganglia and is involved in adaptive control of behaviour through the selection of relevant informations. Dopaminergic neurons that innervate striatum die in Parkinson disease, leading to inefficient adaptive behaviour. Neuronal activity of striatal medium spiny neurons (MSN) is modulated by dopamine receptors. Although dopamine signalling had received substantial attention, consequences of dopamine depletion on MSN intrinsic excitability remain unclear. Here we show, by performing perforated patch clamp recordings on brain slices, that dopamine depletion leads to an increase in MSN intrinsic excitability through the decrease of an inactivating A-type potassium current, IA. Despite the large decrease in their excitatory synaptic inputs determined by the decreased dendritic spines density and the increase in minimal current to evoke the first EPSP, this increase in intrinsic excitability resulted in an enhanced responsiveness to their remaining synapses, allowing them to fire similarly or more efficiently following input stimulation than in control condition. Therefore, this increase in intrinsic excitability through the regulation of IA represents a form of homeostatic plasticity allowing neurons to compensate for perturbations in synaptic transmission and to promote stability in firing. The present observations show that this homeostatic ability to maintain firing rates within functional range also occurs in pathological conditions, allowing stabilizing neural computation within affected neuronal networks.
Journal of Neuroscience, 2010
A correct interplay between dopamine (DA) and glutamate is essential for corticostriatal synaptic plasticity and motor activity. In an experimental model of Parkinson's disease (PD) obtained in rats, the complete depletion of striatal DA, mimicking advanced stages of the disease, results in the loss of both forms of striatal plasticity: long-term potentiation (LTP) and long-term depression (LTD). However, early PD stages are characterized by an incomplete reduction in striatal DA levels. The mechanism by which this incomplete reduction in DA level affects striatal synaptic plasticity and glutamatergic synapses is unknown. Here we present a model of early PD in which a partial denervation, causing mild motor deficits, selectively affects NMDA-dependent LTP but not LTD and dramatically alters NMDA receptor composition in the postsynaptic density. Our findings show that DA decrease influences corticostriatal synaptic plasticity depending on the level of depletion. The use of the TAT2A cell-permeable peptide, as an innovative therapeutic strategy in early PD, rescues physiological NMDA receptor composition, synaptic plasticity, and motor behavior.
Dopamine and synaptic plasticity in the neostriatum
Journal of Anatomy, 2000
After the unilateral destruction of the dopamine input to the neostriatum there are enduring changes in rat behaviour. These have been ascribed to the loss of dopamine and the animals are often referred to as ' hemiparkinsonian '. In the denervated neostriatum, we have shown that not only are the tyrosine hydroxylase positive boutons missing, but also the medium sized densely spiny output cells have fewer spines. Spines usually have asymmetric synapses on their heads. In a recent stereological study we were able to show that there is a loss of approximately 20 % of asymmetric synapses in the lesioned neostriatum by 1 mo after the lesion. Current experiments are trying to establish the specificity of this loss. So far we have evidence suggesting that there is no obvious preferential loss of synapses from either D1 or D2 receptor immunostained dendrites in the neostriatum with damaged dopamine innervation. These experiments suggest that dopamine is somehow necessary for the maintenance of corticostriatal synapses in the neostriatum. In a different series of experiments slices of cortex and neostriatum were maintained in vitro in such a way as to preserve at least some of the corticostriatal connections. In this preparation we have been able to show that cortical stimulation results in robust excitatory postsynaptic potentials (EPSPs) recorded from inside striatal neurons. Using stimulation protocols derived from the experiments on hippocampal synaptic plasticity we have shown that the usual consequence of trains of high frequency stimulation of the cortex is the depression of the size of EPSPs in the striatal cell. In agreement with similar experiments by others, the effect seems to be influenced by NMDA receptors since the unblocking of these receptors with low Mg ++ concentrations in the perfusate uncovers a potentiation of the EPSPs after trains of stimulation. Dopamine applied in the perfusion fluid round the slices has no effect but pulsatile application of dopamine, close to the striatal cell being recorded from, and in temporal association with the cortical trains, leads to a similar LTP like effect. The reduction of K + channel conductance in the bath with TEA also has the effect of making cortical trains induce potentiation of corticostriatal transmission. TEA applied only to the cell being recorded from has no similar effect ; the cortical stimulation again depresses the EPSP amplitude, so the site of action of TEA may well be presynaptic to the striatal cell. The morphological and physiological experiments may not necessarily be related but it is tempting to suggest that dopamine protects some corticostriatal synapses by potentiating them but that in the absence of dopamine others simply disconnect and are no longer detectable on electron microscopy.